Nowadays the relationship of molecular diagnosis and therapeutic effects on cancer is being shown clinically by the appearance of tyrosine kinase inhibitors Iressa and Tarceva. As a result, the concept of drug administration to eligible patients stratified by molecular diagnosis is spreading.
A ROS1 kinase was identified as a human ortholog of e-ros, which is an oncogene of avian sarcoma virus UR2 (University of Rochester 2) (non-patent literature 1). ROS1 gene translocation was first found in glioblastoma, and its fusion partner was FIG (Fused in glioblastoma) (non-patent literature 2). The expression of full-length wild-type ROS1 has been observed in epithelial cells of a wide range of tissues, and a relationship with cancer has also been suggested. It is known that the ROS1 kinase activity becomes constitutive by the fusion of ROS1 with FIG, and that malignant transformation of cells which express the fusion occurs, and cancer occurs in a transgenic mouse with the fusion (non-patent literature 3).
It was reported that fusion genes of CD74 or SLC34A2 with ROS1 were present in non-small cell lung cancer (non-patent literature 4; the term “ROS” is used in non-patent literature 4 instead of “ROS1”). Because CD74-ROS1 was identified in 1 case from 150 patient specimens, and SLC34A2-ROS1 was identified in 1 case from 41 cell lines, the actual frequency in patients and the clinical characteristics of patients are unknown. The fusion site in the CD74-ROS1 gene which was reported in non-patent literature 4 was within exon 6 of the CD74 gene and exon 34 of the ROS1 gene, and no fusions were found in the other exons, and oncogenic potential was not shown. The fusion site of CD74ex6-ROS1ex32 which was found in the present invention is within exon 6 of the CD74 gene and exon 32 of the ROS1 gene. Further, the fusion sites in the SLC34A2-ROS1 gene which was reported in non-patent literature 4 were within exon 4 of the SLC34A2 gene and exon 32 or 34 of the ROS1 gene, and no fusions were found in the other exons. The fusion site of SLC34A2ex13-ROS1ex32 which was found in the present invention is within exon 13 of the SLC34A2 gene and exon 32 of the ROS1 gene.